18-79396207-CCCG-C

Variant names:

• chr18-79396207-CCCG-C
• rs565670974
• NM_001278669.2:c.-7_-5delCGC

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001278669.2(NFATC1):​c.-7_-5delCGC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000147 in 1,466,532 control chromosomes in the GnomAD database, with no homozygous occurrence. There is a variant allele frequency bias in the population database for this variant (GnomAdExome4), which may indicate mosaicism or somatic mutations in the reference population data. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00016 (0 hom.)
• Consequence: NFATC1 NM_001278669.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.279
• Publications: 0 publications found

Genes affected

NFATC1 (HGNC:7775): (nuclear factor of activated T cells 1) The product of this gene is a component of the nuclear factor of activated T cells DNA-binding transcription complex. This complex consists of at least two components: a preexisting cytosolic component that translocates to the nucleus upon T cell receptor (TCR) stimulation, and an inducible nuclear component. Proteins belonging to this family of transcription factors play a central role in inducible gene transcription during immune response. The product of this gene is an inducible nuclear component. It functions as a major molecular target for the immunosuppressive drugs such as cyclosporin A. Multiple alternatively spliced transcript variants encoding distinct isoforms have been identified for this gene. Different isoforms of this protein may regulate inducible expression of different cytokine genes. [provided by RefSeq, Jul 2013]

NFATC1 Gene-Disease associations (from GenCC):

• congenital heart disease

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001278669.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NFATC1	NM_001278669.2	MANE Select	c.-7_-5delCGC		5_prime_UTR	Exon 1 of 10	NP_001265598.1	O95644-1
	NFATC1	NM_006162.5		c.-7_-5delCGC		5_prime_UTR	Exon 1 of 10	NP_006153.2
	NFATC1	NM_172390.3		c.-7_-5delCGC		5_prime_UTR	Exon 1 of 8	NP_765978.1	O95644-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NFATC1	ENST00000427363.7	TSL:1 MANE Select	c.-7_-5delCGC		5_prime_UTR	Exon 1 of 10	ENSP00000389377.2	O95644-1
	NFATC1	ENST00000253506.9	TSL:1	c.-7_-5delCGC		5_prime_UTR	Exon 1 of 10	ENSP00000253506.5	O95644-4
	NFATC1	ENST00000591814.5	TSL:1	c.-7_-5delCGC		5_prime_UTR	Exon 1 of 8	ENSP00000466194.1	O95644-2

Frequencies

GnomAD3 genomes AF: 0.0000198 AC: 3 AN: 151426 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000484

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000658

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000380 AC: 55 AN: 144692 AF XY: 0.000317

Gnomad AFR exome AF: 0.000204

Gnomad AMR exome AF: 0.000938

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000666

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000356

Gnomad OTH exome AF: 0.000911

GnomAD4 exome AF: 0.000161 AC: 212 AN: 1314998 Hom.: 0 AF XY: 0.000181 AC XY: 118 AN XY: 652062

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000755 AC: 2 AN: 26482

American (AMR) AF: 0.000714 AC: 23 AN: 32194

Ashkenazi Jewish (ASJ) AF: 0.000325 AC: 7 AN: 21570

East Asian (EAS) AF: 0.000471 AC: 13 AN: 27628

South Asian (SAS) AF: 0.000287 AC: 21 AN: 73126

European-Finnish (FIN) AF: 0.000174 AC: 8 AN: 46018

Middle Eastern (MID) AF: 0.000997 AC: 4 AN: 4012

European-Non Finnish (NFE) AF: 0.000119 AC: 123 AN: 1032064

Other (OTH) AF: 0.000212 AC: 11 AN: 51904

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0000198 AC: 3 AN: 151534 Hom.: 0 Cov.: 31 AF XY: 0.0000270 AC XY: 2 AN XY: 74072

African (AFR) AF: 0.0000482 AC: 2 AN: 41462

American (AMR) AF: 0.0000657 AC: 1 AN: 15226

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5132

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10368

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67748

Other (OTH) AF: 0.00 AC: 0 AN: 2106

Alfa AF: 0.000381 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.28
Mutation Taster		=297/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs565670974; hg19: chr18-77156207;